Uncontrolled high cortisol in pregnancy may increase women’s risk of diabetes
New analysis also finds greater risk of early birth for these moms' babies
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Pregnant women with Cushing’s syndrome and uncontrolled high levels of cortisol, a naturally occurring steroid hormone, may have a greater risk of developing high blood pressure and diabetes, and their babies are more likely to be born early.
That’s according to the findings of a systematic review and meta-analysis of published studies spanning more than 70 years, conducted by researchers in Brazil.
Specifically, across 16 studies, nearly one-quarter of pregnant women with high cortisol levels, known as hypercortisolism, saw “worsening of preexisting diabetes or development of gestational diabetes,” a type of high blood sugar that develops during pregnancy, the researchers found. Almost 40% of women across 19 studies had conditions related to high blood pressure during pregnancy, the data showed.
The analyses also demonstrated that hypercortisolism in expectant mothers significantly increased the risk for their babies to be born preterm, or before 37 completed weeks of pregnancy. No association was found, however, for miscarriage or newborn mortality, the team noted.
According to the researchers, these results suggest that “early diagnosis of [Cushing’s syndrome] and effective management aimed at achieving disease control remain important strategies for potentially improving maternal and neonatal outcomes.”
The results were described in “Disease activity and maternal-fetal outcomes in pregnant women with cushing’s syndrome: a systematic review and meta‑analysis,” published in Reviews in Endocrine and Metabolic Disorders.
Cushing’s syndrome refers to conditions whose symptoms are driven by excessive cortisol levels. In most cases, it is caused by tumors in the pituitary gland that produce excess adrenocorticotropic hormone (ACTH), a condition known as Cushing’s disease. ACTH triggers the adrenal glands, located above the kidneys, to produce cortisol.
Less frequently, Cushing’s syndrome is caused by ACTH-producing tumors outside the pituitary gland, known as ectopic Cushing’s, or tumors in the adrenal glands, including some adrenal tumors that lead to Cushing’s exclusively during pregnancy.
Pregnancy in women with Cushing’s is uncommon, however, due to fertility issues. When individuals with Cushing’s do conceive, their pregnancies are associated with a higher risk of maternal and fetal complications, earlier studies have shown.
Analysis covered studies from 1953 to 2024
To learn more, the research team conducted a systematic review of maternal and fetal outcomes in pregnancies affected by Cushing’s — particularly focusing on the impact of uncontrolled hypercortisolism.
A total of 22 studies, published between 1953 and 2024 and reporting on 381 pregnancies, were covered in the analysis.
Among 200 women with a reported Cushing’s cause, slighty more than half (54%) had Cushing’s disease. A total of 35% had adrenal tumors, and 2% had been diagnosed with ectopic Cushing’s. Additionally, 5% had Nelson syndrome, when ACTH-producing pituitary tumors develop after surgical removal of both adrenal glands to treat persistent disease.
Of all the women enrolled, 5% had controlled hypercortisolism, according to the scientists.
The mean age of these pregnant women was 30. In 15 studies with available information, 42% of women were diagnosed before pregnancy, 24% during pregnancy, and 34% after giving birth.
Regarding treatment, 11 studies reported the use of medications to control hypercortisolism before and during pregnancies. Four studies reported surgical procedures to treat Cushing’s disease, almost all performed before pregnancy, with one reporting surgery during pregnancy. The overall rate of spontaneous miscarriage was 6%, and that of preterm birth was 37%.
According to the researchers, miscarriages are “surprisingly lower than the frequency described in the general population, which ranges from 10 to 15.3% in different series.” Among possible explanations is low average mother’s age or underreporting of very early pregnancies.
Overall, 39% of pregnant women had high blood pressure (hypertension) disorders of pregnancy, and 24% had worsening of preexisting diabetes or developed gestational diabetes. One thromboembolic event, or the formation of blood clots in the legs or lungs, was reported.
Regarding newborns, 26% were born with low weight and 9% were small for gestational age, or the length of pregnancy. Also, 1% had congenital malformations, and 7% died shortly after birth. The rates of malformations and low birth weight were “lower than those described in the general population, reaching 11% and 27%, respectively,” the researchers wrote.
High cortisol in pregnancy tied to over 7 times higher risk of diabetes
Further meta-analysis of four studies revealed that uncontrolled hypercortisolism was associated with a sixfold higher risk of hypertension during pregnancy and a 7.4 times higher risk for diabetes. It also was linked to about a three times higher risk for preterm birth.
While the results also suggested an association between uncontrolled hypercortisolism and newborn mortality, as well as with miscarriage, the effects were not statistically significant, the researchers noted.
According to the team, these findings show that pregnancy in women with Cushing’s “appears to be associated with an increased risk of adverse maternal and fetal outcomes,” and that “these risks seem to be more frequent in cases of uncontrolled hypercortisolism, in which active disease may exacerbate metabolic and vascular complications.”
The researchers noted that their review and analysis was hampered by small study sizes.
Nonetheless, the team wrote that this new “evidence is essential to improve the understanding of the disease course and to guide clinical management.”
